Polyethylene glycol (PEG) is used in a wide variety of applications including, but not limited to, excipients, plasticizers, softeners, humectants, ointments, polishes, paper coating, lubricants, bases for cosmetics and pharmaceuticals, solvents, binders, metal and rubber processing, and additives to foods and animal feed. Some particular uses of PEG in pharmaceutical applications include, for example, formation of PEG-drug conjugates, treatment of neonatal respiratory distress syndrome, treatment of constipation, treatment of encopresis in children, and diagnosis and therapy of gastrointestinal diseases.
Polyethylene glycol is typically produced by base-catalyzed ring-opening polymerization of ethylene oxide. The reaction is initiated by adding ethylene oxide to a diol in the presence of a catalyst. This process results in a polydispersed mixture of polyethylene glycol polymers with a Poisson distribution centered on the target molecular weight. For example, PEG 400 has a number average molecular weight of around 400, but contains a distribution of oligomers from ethylene glycol to much higher molecular weights; however, when these molecular weights are examined in aggregate the number average molecular weight will be at or around 400. It is generally expected that the number average molecular weight be within five percent of the labeled nominal value for polyethylene glycols with a labeled value of less than 1000 g/mol, within 10% for labeled values between 1000 g/mol and 7000 g/mol and within 12.5% for labeled values greater than 7000 g/mol.
While a majority of the oligomers in a particular polyethylene glycol composition have a molecular weight near the number average molecular weight, compositions typically also contain significant concentrations of lower molecular weight species. And while high molecular weight polyethylene glycol molecules appear to be inert in the body, low molecular weight polyethylene glycol polymers may interact with the human body, especially the liver. Consequently, the concentration of low molecular weight species such as ethylene glycol and diethylene glycol is specified in the United States Pharmacopeia to 0.25% (2,500 ppm) or less with respect to polyethylene glycols having a molecular weight of 1000 g/mol or less for use in fields with application to a living body. Because these low molecular weight polyethylene glycol molecules may interact with the body, polyethylene glycols having reduced concentrations of low molecular weight species would be useful.